Preimplantation Genetic Diagnosis
The Royal Society of Edinburgh (RSE) is pleased to respond to the request by the Human Fertilisation and Embryology Authority and Advisory Committee on Genetic Testing for comments on the consultation document on preimplantation genetic diagnosis (PGD). The RSE is Scotland’s premier Learned Society, comprising Fellows elected on the basis of their distinction, from the full range of academic disciplines, and from industry, commerce and the professions. This response has been compiled with the assistance of a number of Fellows with expertise in this area.
Overall, the consultation document presents a balanced and comprehensive coverage of the issues raised by PGD. It should be noted that with the Human Genome Project nearing completion, the identification of genes responsible for an increasing variety of conditions, or for responsiveness to the environment or medications, will greatly increase the conditions for which PGD might be used. Further, as advances take place in science and medical technology, it is likely that less invasive tests will become available. The speed of advances in this area of medicine has consistently been underestimated and legislation should, therefore, anticipate the time when less invasive, more accurate methods are available.
In all instances, however, where the procedure is carried out it will be essential that prospective parents are advised of the ethical dimensions of the choices which they will be required to make. The ability to diagnose genetic disorders at present exceeds the ability to treat them, and those embryos which are diagnosed as having a genetic disorder will, in many instances, be destroyed.
The specific questions raised in the consultation document are addressed below:
Do you agree with the proposal that, subject to appropriate clinical considerations, the current practice of licensing clinics to perform PGD for a limited number of specific serious inherited conditions, including sex linked disorders and chromosome abnormalities should continue? (Paragraph 28)
The RSE believes that the general answer to this question is yes, and that the current licensing system ensures that only adequately trained people with access to appropriate facilities can offer this service to patients. It will be important, however, that the list of specific conditions is regularly reviewed, and that full attention is given to provision for advice on the ethical dimensions of choices to be made. Research should also be undertaken in order to develop alternative procedures which would not involve the destruction of the embryo, for example in the development of diagnostic techniques involving gametes, that is, ova and spermatozoa.
It is not clear, however, on what basis there should be restrictions of PGD to only serious clinical conditions, although there may be practical reasons for wishing to do so. If there are clinical reasons for undertaking PGD at all - and given that the consultation document itself notes in paragraph 26 that few people are likely to choose it - there appears to be little logic in limiting its use to certain conditions. Of course, this balance might change if it became clear that PGD caused significant harm in large numbers of cases. The balance would then perhaps shift towards not permitting it in 'minor' clinical conditions because of the greater harm caused by using it - namely the additional damage to, or destruction of, the embryo. However, it should also be borne in mind that restricting PGD to serious conditions might mean that the (arguably) ethically less troubling option of non-implantation would be subject to more rigorous controls than the (arguably) more troubling ethical option of pregnancy termination with prenatal diagnosis (PND).
In due course should there be restrictions on who might have access to PGD? (Paragraph 30)
Depending on the weight to be given to reproductive choice, it may be suggested that preventing people from having access to PGD is to restrict a valued liberty. People may already be denied access to in vitro fertilisation (IVF), for example, dueto financial constraints as to which test and which group of people should be offered this as part of local health authority policies. However, if the assumption in paragraph 26 is correct - namely that PGD would seldom be used - then the practical problems are ameliorated. Focus could be made on those patients who are receiving IVF anyway because of infertility, or those who have pre-existing genetic disorder in the family and wish to avoid the birth of an affected child
A more important question might be 'When should fertile people with a history of genetic problems be allowed access to IVF, for the purposes of having access to PGD?'. This seems to be a central question, and following from it also comes the question of whether or not these people should be prioritised for treatment, since presumably the fact of existing fertility might raise their chances of a successful pregnancy following IVF.
Should the seriousness of a genetic condition be a matter of clinical judgement based on general guidance? If so, what aspects might such general guidance cover?(Paragraph 35)
Yes, the seriousness of a genetic condition should be a matter of clinical judgement based on general guidance. Judgements of seriousness and general ethical guidance should be informed by considerations of the consequential corrective surgery and transplantation.
One general principle is that criteria of seriousness should not be harsher for PGD than they are for PND or termination of pregnancy. If it is regarded as ethically acceptable to offer PND and termination of pregnancy in the second trimester for a specified condition, then it would seem ethically acceptable to screen embryos for the same disorder. Indeed, it could be argued that the criteria of seriousness for PND and termination of pregnancy should be stricter than those for PGD, given the greater stage of development of a second trimester foetus.
In addition, with reference to the criteria for a termination of pregnancy for foetal abnormality published by the Royal College of Obstetricians and Gynaecologists, (particularly those sections covering termination on 'social' grounds'), if the condition, however 'non-serious', is likely to affect the emotional health of the woman, it would be illogical if the patient was precluded from making that decision before a pregnancy was established, yet effectively permitted to make it during a pregnancy. This is a matter for patients (and their partners) to make - namely, whether to seek PGD (all else being equal) and what to do with the outcome.
Have you any comments on the general issue of replacing carrier embryos? (Paragraph 36)
Given that carrier status is substantially irrelevant unless and until a decision to reproduce is made, it would be improper to test for carrier status, especially since such testing could be done at the stage when having children is contemplated. On this basis, the decision whether or not to implant carriers should not have to be taken. If, however, detecting carrier status is unavoidable, then again it should be a decision for the woman and her partner, in conjunction with the appropriate counselling, as only they can measure the effect on their lives that having such a child would have. However, given that the embryo is healthy, this is a difficult line to pursue and is best avoided - if technically possible - by not undertaking such tests in the first place. This is not a limitation on the rights of the intending parents – rather, it is a recognition of the irrelevance of the test results themselves, except in very limited - and future - decisions, which can and should be taken by the child itself once adult. There is always the hope that by the time the child is itself able to procreate, gene therapy will be available to correct the condition.
As the commitment to not using embryos casually is, as the Consultation Document itself notes, deeply enshrined in the legislative framework, and especially if PGD may prove potentially harmful to the embryo, it is arguably not within the spirit of the regulation to permit non-essential, indeed non-informative, tests to be undertaken.
Can the principle of the Welfare of the Child ever be compatible with the decision to begin a pregnancy knowing that a child will be born with a genetic disorder? (Paragraph 38)
On one interpretation of the welfare provisions of s. 13(5) of the Human Fertilisation and Embryology Act 1990, the welfare issue relates to the actual environment of a child once born, even although decision makers are required to consider it before conception. If 'welfare' for these purposes is taken to include a state of perfect genetic health, then it must be said that the welfare of the child could not be compatible with deliberately being allowed to be born with a positively detected genetic defect (at least where that defect is likely to cause harm, however defined). However, the converse of this would be the argument that being alive is a benefit - indeed, both contributes to and defines 'welfare' - and that therefore a decision not to implant is a harm (albeit to an entity with no legal status). However, the embryo of the human species is accorded some moral status, which makes this a very difficult issue.
In addition, if it is deemed to breach the welfare provision to bring such a child into the world, there is a real danger that the fear of disvaluing those already born with the condition - noted in paragraph 20 of the Document - might be more likely to become relevant. Moreover, this too is a matter which cannot be divorced from the rights of potential parents to make their own decisions about reproductive matters. The decision here is of the same order as that for a couple undergoing prenatal diagnosis who choose not to opt for termination of pregnancy when the foetus is identified as having a genetic predisposition to a disorder. No women should be forced to have an affected embryo replaced, but equally, medical practitioners should not prevent a woman who makes an informed choice to have such an embryo replaced, particularly if she is relatively infertile and if all the embryos resulting from this particular cycle of IVF appear to be affected and this is her only chance of having a child. As with the case of prenatal diagnosis, knowing that a child will be affected in advance may allow time for the parents to accept and plan for the birth and future of the child.
It is suggested that if a disorder is of late onset, this should be one of a number of factors, but not an overriding factor, in determining whether PGD should be offered. Do respondents consider this to be the correct approach? (Paragraph 45)
The approach outlined is correct. The time of onset of the disease associated with the genetic disorder, its penetrance and inevitability will be factors which the patientand the clinician will consider when deciding whether PGD should be offered. While the extent of an individual life may be limited, the quality of the life of the individual cannot itself be measured.
However, when there is no way of knowing whether the condition will ever manifest itself, depending upon the social and environmental hazards which will confront the individual, nor the severity of the condition if it should appear, nor whether there might be a therapy available before the condition manifests itself, it would be presumptuous to make assumptions about suitability for implantation. Under these circumstances this issue is much more sensitive than many of the others, unless the probability of the onset of a late onset condition is taken to be irrelevant. If this were the approach taken, then no tests for such unpredictable disorders should be available. If not, and despite the fact that the outcome would likely be to discard embryos which have a real chance of a healthy (albeit curtailed) life expectancy, then the decision should rest with the intending parent(s).
Should guidance distinguish between PGD for genes that are highly predictive of a serious disorder and those where the genetic component is more complex? Should the use of PGD for any indication be the subject of clinical judgement, and as such left to practitioners and individual patients to decide? (Paragraph 47)
Guidance should distinguish between the certainties and the predispositions but the decisions should be left to practitioner and patient. In particular it is the patient who will have to live with the knowledge of their decision on behalf of their offspring and conjointly live with the consequences throughout childhood, adolescence and young adulthood. Incidentally in relation to predispositions and age of onset, some day the Authority will have to confront the problem of serious psychiatric and mental disorders or even personality disorders that may not conventionally be classed as purely "medical disorders" yet nevertheless have a genetic basis or predisposition.
In the context of PGD, and given the current practical limitations, should there be any restrictions on the number and range of tests to be carried out in the absence of a clear genetic or medical indication? (Paragraph 52)
Tests should only be carried out if there are clear genetic or medical indications. There should not be a blanket suite of tests for all genetic disorders. Again, this is the same principle as for many other forms of testing and diagnosis. It is also important that informed consent for diagnosis should make it clear that the fact that an embryo does not have a specified genetic disorder does not mean it will be a 'normal healthy child', since it may well have other genetic or other chromosomal disorders which have not been tested for, added to which there is always the risk of damage during delivery.
Should centres be licensed for PGD in general or in relation to each specific test and condition? Should the HFEA record each new condition, mutation or test carried out by individual centres? (Paragraph 58)
Centres should be licensed for each specific test and the HFEA should ensure that licensed clinics are competent to carry out the procedure and have adequate mechanisms for ensuring quality control. HFEA should record any change in what is available and justification must be vigorous and regular and thorough audits undertaken.
Do respondents think that the general approaches proposed for the regulation of PGD are appropriate? (Paragraph 60)
Yes, but there will be need for regular reviews as genetic knowledge and technical expertise develop.
In responding to this inquiry the Society would like to draw attention to the following Royal Society of Edinburgh responses which are of relevance to this subject: Animal Tissue into Humans (April 1997); Consent and the Law (December 1997); Cloning Issues in Reproduction, Science and Medicine (April 1998); Review of the Common Law Provisions Relating to the Removal of Gametes and of the Consent Provisions in the Human Fertilisation and Embryology Act 1990 (April 1999) and Chief Medical Officer’s Expert Group on Cloning (November 1999).